INCREASE IN EXPRESSION LEVELS OF INTERFERON-INDUCIBLE GENES IN SENESCENT HUMAN-DIPLOID FIBROBLASTS AND IN SV40-TRANSFORMED HUMAN FIBROBLASTS WITH EXTENDED LIFE-SPAN

The normal human fibroblast line, TIG-3 which senesces at around 80 po pulation doubling levels (PDLs), expressed interferon (IFN)-inducible genes such as 6-16, 2', 5'-oligoadenylate synthetase (2,5-A) and HLA B 7 near the end of the proliferative lifespan. Other normal fibroblast line such as MRC-5 also expressed IFN-inducible genes when senesced. C lones transformed with SV40 T-antigen, which extended their proliferat ive lifespan by about 20-30 PDLs, also expressed IFN-inducible genes d uring their extended life. Anti-IFN-beta antibodies added in culture m edium repressed the expression of IFN-inducible gene in both senescent and life-extended SV40-transformed IFN-beta repressed DNA synthesis i n normal TIG-3 and induced IFN-inducible genes in both normal and SV40 -transformed TIG-3. Conditioned medium recovered from life-extended SV 40-transformed cells contained IFN-beta, but not IFN-alpha, IFN-gamma or TNF-alpha and possessed an activity that inhibited DNA synthesis of young TIG-3. Addition of anti-IFN-beta antibodies into the medium enh anced the serum-induced DNA synthesis of near senescent (91% lifespan completed) TIG-3, while it neither induced DNA synthesis in fully sene scent TIG-3 nor extended the proliferative lifespan of TIG-3. These re sults suggest that normal and SV40-transformed human fibroblasts incre ase expression of IFN-beta with increasing proliferative age especiall y near the end of their lifespan resulting in induction of IFN-inducib le genes and possibly in growth repression.